Bilateral Subthalamic Stimulation Research Articles

Comparison of Apathy and Cognitive Symptoms in Pre- and Postoperative Period in Deep Brain Stimulation Surgery.

The aim of the study was to investigatie apathy and cognitive functions in Parkinson's disease patients who underwent deep brain stimulation surgery on bilateral subthalamic nuclei. This study included 18 patients with Parkinson's disease who were accommodated in the Parkinson's and Movement Disorders Center of Adana City Training and Research Hospital for treatment in 2022. Patients were evaluated by psychiatry, neurology and neurosurgery specialists with a multidisciplinary approach and found to be surgically appropriate. Standardized Mini-Mental Test and Montreal Cognitive Assessment Scale, Apathy Evaluation Scale, and Hamilton Anxiety and Depression Scale were administered to each patient before the operation and at 6 months after effective stimulation parameters were reached. The mean apathy score at the preoperative zeroth month was 47.77 ± 15.83 in patients having deep brain stimulation surgery and 30.83 ± 13.59 in the postoperative sixth month. Statistically that reduction was significant (P = .003) and showed clinical development. The average Hamilton Anxiety Scale scores at the preoperative zeroth month was 11.50 ± 5.14 and 10.22 ± 5.57 at the postoperative sixth month, with no clinical significance (P = .280). The determined value for the Unified Parkinson's Disease Rating Scale, on treatment, was 22.55 ± 7.53 in the preoperative zeroth month and 14.50 ± 6.99 in the postoperative sixth month, with statistical significance (P < .001). The Unified Parkinson's Disease Rating Scale, off treatment, score was revealed to be significant in the preoperative zeroth month (37.44 ± 9.85) in comparison to that of the postoperative sixth month (23.44 ± 7.86; P < .001). This study showed that bilateral subthalamic stimulation improves nonmotor and motor symptoms in patients having Parkinson's disease. The mechanism is complex, and we believe that future studies focusing on pharmacological and nonpharmacological treatments involving more patient groups will be useful for clinicians.

Septum Pellucidum Cyst in Patient with Parkinson’s Disease-minimally Invasive Staged Therapy

Background: The aim of the case report is to present the minimally invasive staged treatment of a patient with motor complications of Parkinson’s disease with a large septum pellucidum cyst.&#x0D; Material and Method: A two-stage surgical strategy was proposed by the movement disorders team: neuroendoscopic cyst fenestration with subsequent implantation of deep brain stimulation electrodes (subthalamic nucleus) depending on the effect of neuroendoscopic treatment.&#x0D; Results: Despite the technical success of a neuroendoscopic cyst fenestration, as evidenced by a reduction in cyst volume, intraoperative ventriculocystography and postoperative CT showing free communication between the cyst and the ventricular system the motor symptoms caused by Parkinson’s disease remained unchanged. A bilateral subthalamic deep brain stimulation system was implanted with good functional results as documented by her UPRDS III score in the off-medication state (52 points preoperative and 34 point after 6 years postoperative) and reduction of L-DOPA equivalent dose (60% of the pre-deep brain stimulation level). &#x0D; Conclusion: Minimally invasive therapy-neuroendoscopic cyst fenestration, followed by a bilateral subthalamic stimulation implantation-led to the substantial and lasting improvement of the patient’s symptoms.&#x0D;

Clinical parameters predict the effect of bilateral subthalamic stimulation on dynamic balance parameters during gait in Parkinson's disease.

We investigated the effect of deep brain stimulation on dynamic balance during gait in Parkinson's disease with motion sensor measurements and predicted their values from disease-related factors. We recruited twenty patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least 12 months and 24 healthy controls. Six monitors with three-dimensional gyroscopes and accelerometers were placed on the chest, the lumbar region, the two wrists, and the shins. Patients performed the instrumented Timed Up and Go test in stimulation OFF, stimulation ON, and right- and left-sided stimulation ON conditions. Gait parameters and dynamic balance parameters such as double support, peak turn velocity, and the trunk's range of motion and velocity in three dimensions were analyzed. Age, disease duration, the time elapsed after implantation, the Hoehn-Yahr stage before and after the operation, the levodopa, and stimulation responsiveness were reported. We individually calculated the distance values of stimulation locations from the subthalamic motor center in three dimensions. Sway values of static balance were collected. We compared the gait parameters in the OFF and stimulation ON states and controls. With cluster analysis and a machine-learning-based multiple regression method, we explored the predictive clinical factors for each dynamic balance parameter (with age as a confounder). The arm movements improved the most among gait parameters due to stimulation and the horizontal and sagittal trunk movements. Double support did not change after switching on the stimulation on the group level and did not differ from control values. Individual changes in double support and horizontal range of trunk motion due to stimulation could be predicted from the most disease-related factors and the severity of the disease; the latter also from the stimulation-related changes in the static balance parameters. Physiotherapy should focus on double support and horizontal trunk movements when treating patients with subthalamic deep brain stimulation.

Factors affecting postural instability after more than one-year bilateral subthalamic stimulation in Parkinson's disease: A cross-sectional study.

BackgroundBalance impairment in Parkinson’s disease is multifactorial and its changes due to subthalamic stimulation vary in different studies.ObjectiveWe aimed to analyze the combination of predictive clinical factors of balance impairment in patients with Parkinson’s disease treated with bilateral subthalamic stimulation for at least one year.MethodsWe recruited 24 patients with Parkinson’s disease treated with bilateral subthalamic stimulation and 24 healthy controls. They wore an Opal monitor (APDM Inc.) consisting of three-dimensional gyroscopes and accelerometers in the lumbar region. We investigated four stimulation conditions (bilateral stimulation OFF, bilateral stimulation ON, and unilateral right- and left-sided stimulation ON) with four tests: stance on a plain ground with eyes open and closed, stance on a foam platform with eyes open and closed. Age, disease duration, the time elapsed after implantation, levodopa, and stimulation responsiveness were analyzed. The distance of stimulation location from the subthalamic motor center was calculated individually in each plane of the three dimensions. We analyzed the sway values in the four stimulation conditions in the patient group and compared them with the control values. We explored factor combinations (with age as confounder) in the patient group predictive for imbalance with cluster analysis and a machine‐learning‐based multiple regression method.ResultsSway combined from the four tasks did not differ in the patients and controls on a group level. The combination of the disease duration, the preoperative levodopa responsiveness, and the stimulation responsiveness predicted individual stimulation-induced static imbalance. The more affected patients had more severe motor symptoms; primarily, the proprioceptive followed by visual sensory feedback loss provoked imbalance in them when switching on the stimulation.ConclusionsThe duration of the disease, the severity of motor symptoms, the levodopa responsiveness, and additional sensory deficits should be carefully considered during preoperative evaluation to predict subthalamic stimulation-induced imbalance in Parkinson’s disease.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial.

Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. Randomized, double-blinded, double-crossover trial. In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided amplitude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P=0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P=0.024, uncorrected). Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Frequency-specific network activity predicts bradykinesia severity in Parkinson’s disease

ObjectiveBradykinesia has been associated with beta and gamma band interactions in the basal ganglia-thalamo-cortical circuit in Parkinson’s disease. In this present cross-sectional study, we aimed to search for neural networks with electroencephalography whose frequency-specific actions may predict bradykinesia. MethodsTwenty Parkinsonian patients treated with bilateral subthalamic stimulation were first prescreened while we selected four levels of contralateral stimulation (0: OFF, 1–3: decreasing symptoms to ON state) individually, based on kinematics. In the screening period, we performed 64-channel electroencephalography measurements simultaneously with electromyography and motion detection during a resting state, finger tapping, hand grasping tasks, and pronation-supination of the arm, with the four levels of contralateral stimulation. We analyzed spectral power at the low (13–20 Hz) and high (21–30 Hz) beta frequency bands and low (31–60 Hz) and high (61–100 Hz) gamma frequency bands using the dynamic imaging of coherent sources. Structural equation modelling estimated causal relationships between the slope of changes in network beta and gamma activities and the slope of changes in bradykinesia measures. ResultsActivity in different subnetworks, including predominantly the primary motor and premotor cortex, the subthalamic nucleus predicted the slopes in amplitude and speed while switching between stimulation levels. These subnetwork dynamics on their preferred frequencies predicted distinct types and parameters of the movement only on the contralateral side. DiscussionConcurrent subnetworks affected in bradykinesia and their activity changes in the different frequency bands are specific to the type and parameters of the movement; and the primary motor and premotor cortex are common nodes.

Spinal Surgery after Bilateral Subthalamic Stimulation for Patients with Parkinson's Disease: A Retrospective Outcome Analysis of Pain and Functional Control.

Parkinson’s disease (PD) patients often suffer from spinal diseases requiring surgeries, although the risk of complications is high. There are few reports on outcomes after spinal surgery for PD patients with deep brain stimulation (DBS). The objective of this study was to explore the data on spinal surgery for PD patients with precedent DBS. We evaluated 24 consecutive PD patients with 28 spinal surgeries from 2007 to 2017 who received at least a 2-year follow-up. The characteristics and outcomes of PD patients after spinal surgery were compared to those of 156 non-PD patients with degenerative spinal diseases treated in 2013–2017. Then, the characteristics, outcomes, and spinal alignment of PD patients receiving DBS were analyzed in degenerative spinal/lumbar diseases. The mean age at the time of spinal surgery was 68 years. The Hoehn and Yahr score regarding PD was stage 1 for 8 patients, stage 2 for 2 patients, stage 3 for 8 patients, stage 4 for 10 patients, and stage 5 for 0 patient. The median preoperative L-DOPA equivalent daily dose was 410 mg. Thirteen patients (46%) received precedent subthalamic nucleus (STN) DBS. Lumbar lesions with pain were common, and operation and anesthesia times were long in PD patients. Pain and functional improvement of PD patients persisted for 2 years after surgery with a higher complication rate than for non-PD patients. PD patients with STN DBS maintained better lumbar lordosis for 2 years after spinal surgery. STN DBS significantly maintained spinal alignment with subsequent pain and functional amelioration 2 years after surgery. The outcomes of spinal surgery for PD patients might be favorably affected by thorough treatment for PD including DBS.

Bilateral Subthalamic Nucleus Theta-Frequency Stimulation Improves Hippocampal-Based Verbal Fluency in Patients with Parkinson's Disease

Bilateral Subthalamic Nucleus Theta-Frequency Stimulation Improves Hippocampal-Based Verbal Fluency in Patients with Parkinson's Disease

A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease

ObjectiveTo explore how subjective and objective sleep parameters respond to bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). MethodsThirty DBS sleep studies were included by searching PubMed, Embase, and the Cochrane Library, and only 21 prospectively designed studies, including 541 patients, were eligible for the main analysis. We evaluated sleep disturbance using 1 objective measurement, polysomnography (PSG), and 4 subjective scales, including PD Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and restless legs syndrome (RLS). We pooled data using the standard mean difference (SMD). The primary outcome was a change in sleep parameters 6 months postoperatively. Outcomes from <12 months to ≥12 months follow-up were compared in the subgroup analysis. Meta-regression was further conducted. ResultsSTN-DBS significantly improved all 4 subjective sleep scales in the 6-month follow-up: ESS (SMD = 0.234), PDSS (SMD = 0.724), PSQI (SMD = 1.374) and RLS (SMD = 1.086), while most PSG parameters remained unchanged, except for shortened rapid eye movement sleep latency (RSL) (SMD = 0.520). In the over-12-month follow-up, improvement persisted in PDSS but not in ESS. Dopamine drug reduction (p = 0.009) and motor improvement (p = 0.036) were correlated with ESS improvement and PDSS improvement, respectively. ConclusionsBilateral STN-DBS continuously improved subjective nocturnal sleep, while its effect on ESS lasted for only 1 year. Medication reduction and motor improvement may contribute to improved daytime sleepiness and better subjective nocturnal sleep, respectively. Except for a shortened RSL, STN-DBS did not change PSG parameters, including sleep efficiency and sleep architecture. RegistrationOpen Science Framework: DOI 10.17605/OSF.IO/3EGRC.

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson\u2019s disease

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and sleep symptoms in Parkinson’s disease (PD). However, the long-term effects of STN-DBS on sleep and its relationship with QoL outcome are unclear.MethodsIn this prospective, observational, multicenter study including 73 PD patients undergoing bilateral STN-DBS, we examined PDSleep Scale (PDSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, -activities of daily living, and -complications (SCOPA-A, -B, -C), and levodopa-equivalent daily dose (LEDD) preoperatively, at 5 and 24 months follow-up. Longitudinal changes were analyzed with Friedman-tests or repeated-measures ANOVA, when parametric tests were applicable, and Bonferroni-correction for multiple comparisons. Post-hoc, visits were compared with Wilcoxon signed-rank/t-tests. The magnitude of clinical responses was investigated using effect size.ResultsSignificant beneficial effects of STN-DBS were observed for PDSS, PDQ-8, SCOPA-A, -B, and -C. All outcomes improved significantly at 5 months with subsequent decrements in gains at 24 months follow-up which were significant for PDSS, PDQ-8, and SCOPA-B. Comparing baseline and 24 months follow-up, we observed significant improvements of PDSS (small effect), SCOPA-A (moderate effect), -C, and LEDD (large effects). PDSS and PDQ-8 improvements correlated significantly at 5 and 24 months follow-up.ConclusionsIn this multicenter study with a 24 months follow-up, we report significant sustained improvements after bilateral STN-DBS using a PD-specific sleep scale and a significant relationship between sleep and QoL improvements. This highlights the importance of sleep in holistic assessments of DBS outcomes.

Functional Outcome of Bilateral Subthalamic Nucleus-Deep Brain Stimulation in Advanced Parkinson's Disease Patients: A Prospective Study.

Background:Deep brain stimulation (DBS) is an accepted modality of treatment in patients with Parkinson's disease (PD). Although DBS was approved in advanced PD, it is being done in early PD as well. It was mainly developed to help the patients of PD to overcome the adverse motor effects associated with treatment and treatment failure.Objective:The objective is to study the efficacy of subthalamic nucleus (STN)-DBS procedure in patients with PD.Materials and Methods:This was a prospective, single-center, follow-up observational study using a direct, structured interview of 40 selected PD patients. Preoperative assessment using Unified PD Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MOCA), and Parkinson's Disease Questionnaire-39 were done. All the patients underwent DBS. Postoperatively, similar assessment was done during follow-up period of 6 months. The results were analyzed using Student's t-test.Results:The total score of UPDRS-III was reduced by 35% after STN-DBS intervention which was statistically significant (P < 0.05). STN-DBS intervention was successful in significantly reducing all UPDRS-III subscores but failed to reduce the scores in case of postural stability. MOCA scores of the patients were not found to be affected by STN-DBS intervention (P = 0.1466). Similar findings were also observed for MOCA subscores, but there was significant improvement of verbal fluency in all patients. Quality of life(QoL) improved significantly in all patients after STN-DBS intervention in all areas. Lower baseline UPDRS-III scores were found to enhance the QoL both in “off” and “on” state. However, prolonged disease duration and older age at PD onset were found to be hampering factors in the improvement of QoL.Conclusions:STN-DBS is a safe procedure and can be performed in all patients of PD who develop disabling motor fluctuations to improve their QoL irrespective early or advanced disease.

Quality of Life as a Predictor of Deep Brain Stimulation Outcome

To define whether quality of life is a predictor of outcomes from bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson disease

EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease.

Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD). In this prospective, multicenter, international, real-life cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics. In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome. This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices. © 2019 International Parkinson and Movement Disorder Society.

Beneficial effects of bilateral subthalamic stimulation on alexithymia in Parkinson's disease.

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non-motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear. In this prospective, observational study of 39 patients with PD undergoing STN-DBS, we examined the Parkinson's Disease Questionnaire-8 (PDQ-8), 20-item Toronto Alexithymia Scale (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self-Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS-II/-III/-IV) and levodopa-equivalent daily dose (LEDD) pre-operatively and at 5-month follow-up. Outcome changes were tested with Wilcoxon signed-rank or paired t-test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ-8 and TAS-20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ-8 improvement were calculated for all baseline parameters. The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN-DBS on PDQ-8, TAS-20, HADS, UPDRS-II, -III and -IV scores and significant LEDD reduction. The correlation between TAS-20 and PDQ-8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ-8 improvement were significant for PDQ-8 and TAS-20. This is the first report of beneficial effects of STN-DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.

The mutual relationship of bilateral subthalamic stimulation impact on the non-motor and motor symptoms in Parkinson’s disease: open, prospective pilot study (P4.065)

The mutual relationship of bilateral subthalamic stimulation impact on the non-motor and motor symptoms in Parkinson’s disease: open, prospective pilot study (P4.065)

Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease.

The objective of this study was to investigate 24-month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN-DBS, we examined the Non-motor Symptom Scale, Non-Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-motor examination, -activities of daily living, and -complications, and levodopa-equivalent daily dose preoperatively and at 5 and 24-month of follow-up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated-measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24-month follow-up were calculated for all outcomes. The Non-motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5-month follow-up. From 5 to 24-month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24-month follow-up, significant improvements were observed for the Non-motor Symptom Scale (small effect), Scales for Outcomes in PD-motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease-complications and levodopa-equivalent daily dose showed large effects. Non-motor Symptom Scale change scores from baseline to 24-month follow-up correlated significantly with Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-activities of daily living, and -motor complications change scores. This study provides evidence of beneficial effects of bilateral STN-DBS on nonmotor symptoms at 24-month follow-up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society.

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p<0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p<0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications. German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic.

The mutual relationship of bilateral subthalamic stimulation initial impact on the non-motor and motor symptoms in Parkinson’s disease - an open prospective study

Background: There are numerous studies which have documented significant improvement in motor symptoms and quality of life in patients with Parkinson’s disease after deep brain stimulation of the sub- thalamic nucleus (STN-DBS). However, relatively little is known about the effects STN-DBS on non-motor symptoms.

Neuropsychological outcomes from constant current deep brain stimulation for Parkinson's disease.

ABSTRACTObjectiveThe aim of this study was to evaluate the neurobehavioral safety of constant‐current subthalamic deep brain stimulation and to compare the neuropsychological effects of stimulation versus electrode placement alone.MethodsA total of 136 patients with Parkinson's disease underwent bilateral subthalamic device implantation in this randomized trial. Patients received stimulation either immediately after device implantation (n = 101; active stimulation) or beginning 3 months after surgery (n = 35; delayed activation control). Patients were administered neuropsychological tests before, 3, and 12 months after device implantation.ResultsNeuropsychological change in stimulation and control groups were comparable. Within‐group analyses revealed declines in category and switching verbal fluency in both groups, but only the stimulation group had letter verbal fluency and Stroop task declines. Depression symptom improvements occurred in both groups, but more often in the stimulation group. Letter fluency declines were associated with worse Parkinson's Disease Questionnaire Communication subscale scores. Baseline and 12‐month comparisons (in the combined group) revealed gains in verbal and visual delayed recall scores and improvement in depression symptoms, but decrements in verbal fluency and Stroop scores.ConclusionsConstant‐current bilateral subthalamic stimulation had a good cognitive safety profile except for decrements in verbal fluency and on the Stroop task. These abnormalities are related to device implantation, but stimulation likely had an additive effect. One year after surgery, the cognitive changes did not exert a detrimental effect on quality of life, although letter fluency declines were associated with communication dissatisfaction at 12 months. Improvement in depressive symptom severity appears dependent on stimulation and not placebo or lesion effects. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.